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ID: ALA1138695

Journal: Bioorg Med Chem Lett

Title: Synthesis of stavudine amino acid ester prodrugs with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS.

Authors: Sriram D, Yogeeswari P, Srichakravarthy N, Bal TR.

Abstract: A series of prodrugs of stavudine were synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS. The 5'-OH function of stavudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide, piperazine and dimethylamine acetic acid. The anti-HIV-1 activity of the esters was determined in CEM cell line and stavudine ester bearing piperazine acetic acid was found to be the most potent compound with a selective index of >15,723. Stavudine prodrug bearing ciprofloxacin and norfloxacin acetic acid showed 100% inhibition against Mycobacterium tuberculosis H(37)Rv at 6.25 microg/mL. The prodrugs also exhibited antibacterial activity against 24 pathogenic bacteria. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterases with t(1/2) ranging from 20-240 min.

CiteXplore: 14980640

DOI: 10.1016/j.bmcl.2004.01.007